Mullerian Inhibiting Substance (MIS) is a glycoprotein produced by the Sertoli cells of the embryonic testis. It is a non-steroidal factor that causes regression of the Mullerian duct, the anlagen of the internal female reproductive tract [Jost, Rec. Prog. Horm. Res., 8, 379-418 (1953)]. MIS, in addition to its important role in development, has been shown to be cytotoxic to the human ovarian tumor cell line HOC-21, both in vitro and in vivo (in a nude mouse model) [Donahoe et al., Science, 205, 913-15 (1979); Fuller et al., J. Clin. Endocrinol. Metab., 54, 1051-55 (1982); Donahoe et al., Ann. Surg., 194, 472-80 (1981)].
Both human MIS and bovine MIS have been cloned and expressed in various bacterial and animal host cells using both genomic and cDNA sequences. The products of such recombinant transformed cells, as well as those of Sertoli cells, are 70K polypeptides which dimerize to form 140K disulfide-linked dimers. The purified dimers from Sertoli cells or recombinant cells (e.g., CHO cells transfected with an MIS gene) are active in vitro in causing regression of the rat Mullerian duct in a standard organ culture assay [Cate et al., Cell, 45, pp. 685-98 (1986)].